ライフサイエンスコーパス: PCSK9

1 oprotein convertase subtilisin-kexin type 9 (PCSK9).

2 oprotein convertase subtilisin/kexin type 9 (PCSK9).

3 oprotein convertase subtilisin/kexin type 9 (PCSK9).

4 actions for known lipid loci such as LPL and PCSK9.

5 otein, and monoclonal antibodies that target PCSK9.

6 sistin-mediated transcriptional induction of PCSK9.

7 on of SREBP2 and subsequent transcription of PCSK9.

8 and resistin lost their ability to activate PCSK9.

9 of leptin and resistin receptors or that of PCSK9.

10 oprotein convertase subtilisin/kexin type 9 (PCSK9), a gene that, when repressed, can lower blood cho

11 oprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein metab

12 oprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipopro

13 We engineered a peptide inhibitor of PCSK9, a target for clinical management of hypercholeste

14 Here we show that inhibiting PCSK9-a key protein in the regulation of cholesterol met

15 lesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in

16 -LDL association in the circulation inhibits PCSK9 activity.

17 oprotein convertase subtilisin/kexin type 9 (PCSK9), adhesion molecules, and clotting and inflammator

18 oprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown.

19 An increasing number of weighted PCSK9 alleles were associated with stepwise lower LDL ch

20 Inhibition of PCSK9 also results in reductions of plasma lipoprotein (

21 ally, we found that for missense SNPs within PCSK9, alterations in both proteolysis and secretion are

22 elations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis

23 of post-treatment with lipoMSN carrying both pcsk9 and angptl3-targeted RNPs, could not be reached wi

24 and familial hypobetalipoproteinemia (FHBL; PCSK9 and APOB).

25 /+) murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis.

26 lesterol, an association between circulating PCSK9 and early as well as advanced stages of atheroscle

27 genetically proxied inhibition of NPC1L1 and PCSK9 and genetically proxied circulating LDL cholestero

28 inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels.

29 Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for

30 ibit the protein-protein interaction between PCSK9 and LDLR.

31 der-to-order transition is a true feature of PCSK9 and not limited to peptides.

32 glucagon action increased hepatic and plasma PCSK9 and resulted in lower LDLR (LDL receptor) protein

33 modulates lipid regulatory genes, including PCSK9 and the LDLR, and also highlights a novel mechanis

34 further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following ora

35 Pcsk9 deficient (pcsk9 (-/-)) and wild-type (WT) littermates underwent pa

36 vels, whereas this response was abrogated in Pcsk9(-/-) and Ldlr(-/-) mice.

37 LOF or nonsynonymous variants in APOB, APOE, PCSK9, and TM6SF2 that are private or enriched in the SW

38 ed to prioritize individual rare variants in PCSK9, ANGPTL4 and CETP in the Action to Control Cardiov

39 Evolocumab and other anti-PCSK9 antibodies reduced adverse cardiovascular outcomes

40 SK9-either through genetic deletion or using PCSK9 antibodies-increases the expression of major histo

41 In this first randomized trial assessing a PCSK9 antibody in the very high-risk setting of ACS, evo

42 tation in the lipid-metabolism-related genes pcsk9, apoc3, and angptl3 would improve cardiovascular h

43 anslation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angio

44 New technologies to inhibit PCSK9 are now being harnessed and might further revoluti

45 lly applying small interfering RNA targeting Pcsk9 as a psoriasis treatment.

46 The linker forms favorable interactions with PCSK9 as evidenced by thermodynamics, structure-activity

47 e polymorphisms (SNPs) in HMGCR, NPC1L1, and PCSK9 associated with low-density lipoprotein (LDL) chol

48 The EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in

49 oprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), pr

50 No mutations were found in either APOB or PCSK9, but nine probands were homozygous for seven diffe

51 compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34,

52 Interestingly, the reduction of PCSK9 can be blocked by the treatment of berberine, a na

53 A pathogenic variant in LDLR, APOB, or PCSK9 can be identified in 30% to 80% of patients with c

54 ed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by

55 Mechanistically, we find that PCSK9 can disrupt the recycling of MHC I to the cell sur

56 We also found that suppressing PCSK9 can significantly alter the cell cycle and induce

57 Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,0

58 PCSK9 concentrations negatively correlated with proinfla

59 ve of this study was to determine effects of PCSK9 deficiency in a mouse model of SCD.

60 oprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency leads to lower cholesterol and is asso

61 oprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice.

62 Pcsk9 deficient (pcsk9 (-/-)) and wild-type (WT) litterm

63 performed from donor SCD mice to wild-type, PCSK9-deficient, and LDLR-deficient recipients to genera

64 NA, indicating that Gcgr signaling regulates PCSK9 degradation.

65 Given that PCSK9 degrades the LDL receptor (LDLR) and prevents the

66 protein involved in cholesterol metabolism, PCSK9, demonstrating the potential utility of these frag

67 on and increases circulating LDL levels in a PCSK9-dependent manner.

68 of AUD showed that alcohol exposure leads to PCSK9 downregulation.

69 Inhibiting PCSK9-either through genetic deletion or using PCSK9 ant

70 es: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evo

71 LASER expression, accompanied with increased PCSK9 expression, suggesting a feedback regulation of ch

72 lished the effect of LASER on HNF-1alpha and PCSK9 expressions.

73 rved quantitative binding of Ab6E2 to native PCSK9 from various cell lines suggests that the disorder

74 l studies have provided molecular details of PCSK9 function.

75 ssociation of an LDL-lowering variant in the PCSK9 gene (T allele of rs1159147), as well as 2 LDL-low

76 epG2 cells, leptin and resistin up-regulated PCSK9 gene and protein expression, as well as the phosph

77 iated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 x

78 Deleting the PCSK9 gene in mouse cancer cells substantially attenuate

79 he proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes.

80 riants in the HMGCR (target for statins) and PCSK9 genes with increased risk of type 2 diabetes melli

81 Therefore, we hypothesized that certain PCSK9 genetic variants may modify the association betwee

82 PCSK9 has a broad repertoire of molecular effects.

83 oprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed to treat hyperlipidemia.

84 oprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular

85 oprotein convertase subtilisin-kexin type 9 (PCSK9) have been shown to reduce LDL cholesterol levels

86 At diet completion, hypercholesterolemic PCSK9-HFD had significantly (P<0.05 versus baseline) dep

87 fat TNF-alpha expression was upregulated in PCSK9-HFD, colocalized with nerve fibers, and correlated

88 et, n=6) or high-fat diet (HFD; WT-HFD, n=3; PCSK9-HFD, n=6).

89 downstream mediators of glucagon's action on PCSK9 homeostasis.

90 Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of

91 ivery of Nme2Cas9 with a guide RNA targeting Pcsk9 in adult mouse liver produces efficient genome edi

92 A, was shown to inhibit hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholeste

93 es are needed to elucidate the exact role of PCSK9 in ALD and alcohol use disorder (AUD) and to evalu

94 diovascular Outcomes Following Inhibition of PCSK9 in Different Populations.

95 We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-ind

96 This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of t

97 man keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis.

98 injection into mice induces >80% editing of Pcsk9 in the liver.

99 Soon after, studies uncovered the role of PCSK9 in the regulation of LDL-receptor recycling and id

100 ed a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; P=0.007)

101 Data on PCSK9 inhibition in chronic kidney disease (CKD) is limi

102 urther Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials

103 urther Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER

104 urther Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreas

105 urther Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing

106 urther Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial r

107 urther Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a rand

108 Further Cardiovascular Outcomes Researh With PCSK9 Inhibition in Subjects With Elevated Risk).

109 meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE.

110 Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE a

111 PCSK9 inhibition significantly reduces the risk of VTE.

112 e full spectrum of potential side effects of PCSK9 inhibition using a genetic approach have not been

113 PCSK9 inhibition with alirocumab attenuated alcohol-indu

114 INTERPRETATION: PCSK9 inhibition with evolocumab significantly reduced c

115 e at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced t

116 ever, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction rema

117 For this reason, the PCSK9 inhibition, by small molecules or peptides, is a v

118 nded to derive greater coronary benefit from PCSK9 inhibition.

119 disease predicted by these same methods for PCSK9 inhibition.

120 statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo.

121 ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patien

122 In this study, we evaluated the PCSK9 inhibitor alirocumab, a monoclonal antibody that r

123 nalysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on car

124 In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab ha

125 This PCSK9 inhibitor is one of many peptides that could benef

126 ht to provide novel bicyclic next-generation PCSK9 inhibitor peptides such as 78.

127 , throughout the longest-duration study of a PCSK9 inhibitor reported to date.

128 from ezetimibe trials, and 3533 (16.4%) from PCSK9 inhibitor trials.

129 therapy; add-on alirocumab therapy, 75 mg (a PCSK9 inhibitor); and uptitration to alirocumab, 150 mg.

130 uced ASCVD mortality rate was reported for 1 PCSK9 inhibitor.

131 ensitivity analyses included evolocumab as a PCSK9 inhibitor.

132 statins plus ezetimibe, and 14% with add-on PCSK9 inhibitor.

133 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in a subset of patients with

134 found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester

135 ognized role in dengue pathogenesis and that PCSK9 inhibitors could be a suitable host-directed treat

136 Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosc

137 algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL

138 urther Cardiovascular Outcomes Research With PCSK9 inhibitors in Subjects With Elevated Risk).

139 The list prices of PCSK9 inhibitors in the United States (>$14,500 per year

140 ials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering ca

141 These PCSK9 inhibitors lowered plasma LDL-C levels by approxim

142 pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted.

143 al patients, the high out-of-pocket costs of PCSK9 inhibitors may impede access and reduce long-term

144 human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.

145 The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggre

146 sterol and have good safety profiles, though PCSK9 inhibitors remain costly.

147 The clinical benefit of PCSK9 inhibitors seen in these trials occurred in the se

148 utcome trials were completed and showed that PCSK9 inhibitors significantly reduce the risk of major

149 ntrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in bo

150 The budgetary impact of PCSK9 inhibitors would be very large if all potentially

151 s need to be looked for in future studies of PCSK9 inhibitors, although we did not find signals that

152 for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1

153 ic analyses suggesting that long-term use of PCSK9 inhibitors, like statins, may be associated with i

154 usses the history and mechanism of action of PCSK9 inhibitors, their metabolic effects, and clinical

155 L receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies chara

156 terol-ester transfer protein inhibitors, and PCSK9 inhibitors.

157 OR, 2.85; 95% CI, 1.34-6.06) with the use of PCSK9 inhibitors.

158 f pharmacotherapies, including ezetimibe and PCSK9 inhibitors; use of lipoprotein apheresis for sever

159 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with persistently elevated

160 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors substantially reduce low-density lipop

161 oprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which both reduce major atherosclerot

162 oprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to statin therapy.

163 One compound (named RIm13) displayed a PCSK9 inhibitory activity 10-fold lower than the templat

164 midazole-based peptidomimetic that has shown PCSK9 inhibitory activity in the micromolar range.

165 ether, these results suggest that inhibiting PCSK9 is a promising way to enhance immune checkpoint th

166 In conclusion, deficiency of PCSK9 is associated with worsened anemia in SCD mice due

167 In human plasma, 30-40% of PCSK9 is bound to LDL particles; however, the physiologi

168 We found that PCSK9 is overexpressed in psoriatic lesions and that sup

169 PCSK9 is predominantly expressed in hepatocytes as a cri

170 PCSK9 is primarily expressed in the liver and regulates

171 Serum Pcsk9 is reduced to undetectable levels, and cholesterol

172 Proprotein convertase subtilisin/kexin 9 (PCSK9) is a key regulator of lipid metabolism by degradi

173 ein convertase subtilisin-like/kexin type 9 (PCSK9) is a key regulator of plasma LDL-cholesterol (LDL

174 oprotein convertase subtilisin/kexin type-9 (PCSK9) is a ligand of low-density lipoprotein (LDL) rece

175 Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of the hepatic

176 and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated m

177 d LDL reported here supports the notion that PCSK9-LDL association in the circulation inhibits PCSK9

178 lternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not.

179 The PCSK9-LDLR axis was associated with outcomes in patients

180 he most potent small molecules targeting the PCSK9/LDLR protein-protein interaction.

181 in DMD mice and significantly decrease serum PCSK9 level in C57BL/6 mice.

182 The median baseline circulating PCSK9 level was 323 ng/mL (interquartile range, 258-406

183 ffect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipi

184 large cardiovascular outcomes trial suppress PCSK9 levels and consistently and substantially reduce L

185 esults suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of

186 To characterize variability in PCSK9 levels and determine whether the LDL-C level reduc

187 ted to CB1R blockade, while the reduction of PCSK9 levels and the related increase in LDLR resulted f

188 vealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR

189 Plasma PCSK9 levels are associated with an increased risk of CV

190 diet-induced steatosis increases circulating PCSK9 levels as a result of de novo expression in mice.

191 Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and

192 In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascul

193 upported by the detection of elevated plasma PCSK9 levels in patients with dengue with high viremia a

194 t LASER is positively correlated with plasma PCSK9 levels in statin free patients.

195 e association between circulating leptin and PCSK9 levels was found only when the body mass index was

196 both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-,

197 substudy from 4 phase 2 trials, circulating PCSK9 levels were measured at baseline and then weekly a

198 Circulating PCSK9 levels were measured at baseline using quantitativ

199 Regardless of baseline PCSK9 levels, the doses of evolocumab being studied in a

200 on achieved with evolocumab differs based on PCSK9 levels.

201 oprotein convertase subtilisin/kexin type 9 (PCSK9) levels correlate positively with liver steatosis

202 oprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240.

203 We investigated the association between PCSK9 LOF variants and neurocognitive impairment and dec

204 ed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% co

205 PCSK9 LOF variants were not associated with incident str

206 PCSK9 LOF variants were not associated with stroke risk.

207 0.05) among participants with versus without PCSK9 LOF variants.

208 PCSK9 loss-of-function (LOF) variants allow for the exam

209 PCSK9 loss-of-function genetic variants were independent

210 ubstitution representing an atheroprotective PCSK9 loss-of-function mutation.

211 PCSK9 loss-of-function resulted in low lipoproteins and

212 PCSK9 loss-of-function, in the context of low lipoprotei

213 PCSK9, low-density lipoprotein, and high-density lipopro

214 putative alpha-helical motif in full-length PCSK9 lowered LDL binding affinity >5-fold.

215 Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG

216 sis was evident in 60% of WT mice and 25% of pcsk9 (-/-) mice (p < 0.05).

217 ular trap formation (NETs) in WT compared to pcsk9 (-/-) mice.

218 Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a saf

219 for understanding the potential benefits of PCSK9 monoclonal antibodies incremental to statins in on

220 The mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism re

221 ab treatment also attenuated alcohol-induced PCSK9 mRNA elevation and upregulated LDL-receptor (LDL-R

222 Gain-of-function PCSK9 mutations associated with familial hypercholestero

223 Furthermore, clinically approved PCSK9-neutralizing antibodies synergize with anti-PD1 th

224 onths of a normal diet (WT-normal diet, n=4; PCSK9-normal diet, n=6) or high-fat diet (HFD; WT-HFD, n

225 y prevented the LDLR degradation mediated by PCSK9 on HepG2 cells.

226 1L1 (OR, 0.97 [95% CI, 0.53-1.75]; P = .91), PCSK9 (OR, 0.98 [95% CI, 0.85-1.13]; P = .80), or circul

227 ed PCSK9 status, SCD mice with deficiency of PCSK9 (Pcsk9(-/-), SCD(bmt)), and SCD mice with deficien

228 Our findings therefore suggest that PCSK9 plays a hitherto unrecognized role in dengue patho

229 Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a

230 oprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plas

231 (APOA5, APOB, APOE, GCKR, IRS-1, LPL, MTHFR, PCSK9, PNPLA3, PPARgamma2), gene-exercise (APOA1, APOA2,

232 owever, the N-terminal acidic stretch of the PCSK9 prodomain (Q31-T60) has eluded structural investig

233 region showed that the two adipokines raised PCSK9 promoter activity via the involvement of a sterol

234 Biological validation showed that PCSK9 promoter methylation is conserved across tissues a

235 The analysis of the human PCSK9 promoter region showed that the two adipokines rai

236 Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) ar

237 Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) in

238 WT (wild type) or PCSK9 (proprotein convertase subtilisin-like/kexin type-

239 PCSK9 (proprotein convertase subtilisin/kexin 9) inhibit

240 though short-term trials have suggested that PCSK9 (proprotein convertase subtilisin/kexin type 9) in

241 d reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) in

242 We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) in

243 PCSK9 (proprotein convertase subtilisin/kexin type 9) in

244 individuals who derive greater benefit from PCSK9 (proprotein convertase subtilisin/kexin type 9) in

245 lesterol) homeostasis through regulating the PCSK9 (proprotein convertase subtilisin/kexin type 9) le

246 Alirocumab, an antibody that blocks PCSK9 (proprotein convertase subtilisin/kexin type 9), w

247 eceptor)-KO (knockout), LDLr-KO/APOB100, and PCSK9 (proprotein convertase subtilisin/kexin type 9)-ov

248 ents raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) in

249 ing proline substitutions in peptides and in PCSK9 protein indicated that Ab6E2 specifically recogniz

250 aled that glucagon affected the half-life of PCSK9 protein without changing the level of its mRNA, in

251 rase readout to evaluate the single-turnover PCSK9 proteolytic event.

252 penhagen City Heart Study were genotyped for PCSK9 R46L (rs11591147), R237W (rs148195424), I474V (rs5

253 id metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease.

254 of proprotein convertase subtilisin/kexin 9 (PCSK9) reduces cardiovascular events and may therefore a

255 cribe a new posttranscriptional mechanism of PCSK9 regulation.

256 ight on allosteric conformational changes in PCSK9 required for high-affinity binding to LDL particle

257 oprotein convertase subtilisin/kexin type 9 (PCSK9), respectively.

258 in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009).

259 ion of FH-associated mutations that diminish PCSK9's ability to bind LDL reported here supports the n

260 , through a mechanism that is independent of PCSK9's cholesterol-regulating functions.

261 o requires a disordered N-terminal region in PCSK9's prodomain.

262 d a complete biochemical characterization of PCSK9's proteolytic function, which could inform therape

263 show that some SNPs allosterically modulate PCSK9's substrate sequence specificity.

264 ron in Pcsk9(-/-), SCD(bmt) mice compared to Pcsk9(+/+), SCD(bmt) mice consistent with greater hemoly

265 wer in Pcsk9(-/-), SCD(bmt) mice compared to Pcsk9(+/+), SCD(bmt) mice, anemia was more severe in Pcs

266 ficient recipients to generate SCD controls (Pcsk9(+/+), SCD(bmt)) with preserved PCSK9 status, SCD m

267 Although cholesterol levels were lower in Pcsk9(-/-), SCD(bmt) mice compared to Pcsk9(+/+), SCD(bm

268 ens, and kidneys contained increased iron in Pcsk9(-/-), SCD(bmt) mice compared to Pcsk9(+/+), SCD(bm

269 +), SCD(bmt) mice, anemia was more severe in Pcsk9(-/-), SCD(bmt) mice.

270 9 status, SCD mice with deficiency of PCSK9 (Pcsk9(-/-), SCD(bmt)), and SCD mice with deficiency of L

271 ment known structural data, and suggest that PCSK9 self-proteolysis is the rate-limiting step of secr

272 ed psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also us

273 Rac1V12(-/+) mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic l

274 ntrols (Pcsk9(+/+), SCD(bmt)) with preserved PCSK9 status, SCD mice with deficiency of PCSK9 (Pcsk9(-

275 ence RNA-based therapeutic targeting hepatic PCSK9 synthesis).

276 l interfering ribonucleic acid that inhibits PCSK9 synthesis.

277 The PCSK9 T allele was significantly (Bonferroni P<6.25x10(-

278 Nominally significant associations of the PCSK9 T allele were also seen with peptic ulcer disease,

279 alysis suggested that the association of the PCSK9 T allele with risk of T2DM but not diastolic blood

280 s a fully human, monoclonal antibody against PCSK9 that reduces low-density lipoprotein cholesterol (

281 and identified loss-of-function variants of PCSK9 that were associated with low circulating levels o

282 ed exploration of potential oral, once-a-day PCSK9 therapeutics for the treatment of cardiovascular d

283 Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, h

284 and to evaluate efficacy and safety of anti-PCSK9 treatment in clinical populations with ALD/AUD.

285 We demonstrated that chronic anti-PCSK9 treatment using the monoclonal antibody alirocumab

286 effective and novel treatments for ALD, anti-PCSK9 treatment with the monoclonal antibody that spares

287 intake and CVD risk.We determined whether a PCSK9 variant (rs11206510), which has been identified fo

288 Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and r

289 INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol wer

290 that genetically low LDL cholesterol due to PCSK9 variation is causally associated with low cardiova

291 Genetically low LDL cholesterol due to PCSK9 variation was causally associated with low risk of

292 The gene encoding PCSK9 was first identified and linked to the phenotype o

293 PCSK9 was significantly decreased after cashew consumpti

294 oprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to have a mutually regulating relation

295 zing rapidity, monoclonal antibodies against PCSK9 were developed and studied in large clinical progr

296 Patients with higher levels of PCSK9 were more likely to be receiving intensive statin

297 We found that HNF-1alpha and PCSK9 were reduced after LASER knock-down.

298 oprotein convertase subtilisin/kexin type 9 (PCSK9), which reduces low-density lipoprotein receptor (

299 PCSK9, which promotes the degradation of low-density lip

300 In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy